Congenital muscular dystrophy: from muscle to brain

Abstract

Congenital muscular dystrophies (CMDs) are a wide group of muscular disorders that manifest with very early onset of muscular weakness, sometime associated to severe brain involvement.The histologic pattern of muscle anomalies is typical of dystrophic lesions but quite variable depending on the different stages and on the severity of the disorder.Recent classification of CMDs have been reported most of which based on the combination of clinical, biochemical, molecular and genetic findings, but genotype/phenotype correlation are in constant progression due to more diffuse utilization of the molecular analysis.In this article, the Authors report on CMDs belonging to the group of dystroglycanopathies and in particular on the most severe forms represented by the Fukuyama CMD, Muscle-Eye-Brain disease and Walker Walburg syndrome.Clinical diagnosis of infantile hypotonia is particularly difficult considering the different etiologic factors causing the lesions, the difficulty in localizing the involved CNS area (central vs. peripheral) and the limited role of the diagnostic procedures at this early age.The diagnostic evaluation is not easy mainly in differentiating the various types of CMDs, and represents a challenge for the neonatologists and pediatricians. Suggestions are reported on the way to reach a correct diagnosis with the appropriate use of the diagnostic means.

Keywords: Brain involvement; Congenital muscle diseases; Fukuyama congenital muscular dystrophy; Muscle-eye-brain disease; Muscular dystrophies; Walker-Warburg syndrome.

Fig. 1

Archive’s photo. Histological features of the patient with WWS showing the typical dystrophic lesions at the beginning of the disease with initial lesions (left) and after 14 months with clear dystrophic features (right)

Fig. 2

Archive’s photo. The same patient. Macroscopic examination, showing severe architectural disarrangement with clear signs of lissencephaly

Fig. 3

A new case of WWS showing severe lissencephaly lesions

Fig. 4

Physical examination of the hypotonic child: “Pull to sit” maneuver

Fig. 5

Physical examination of the hypotonic child: “horizontal suspension” maneuver

Fig. 6

Physical examination of the hypotonic child: “vertical suspension” maneuver

Fig. 7

Infant with early SMA. Note the severe hypotonia, the vivid look, severe involvement of diaphragm, and intercostal muscles

Fig. 8

Severe myotonic dystrophy. Patient born with polyhydramnios with congenital talipes equino-varus responsive to Mestinol

Fig. 9

A girl, 2 years old, affected by nemalinic myopathy